Summary
Glucan, a β1–3-polyglucosidic component of the cell wall of Saccharomyces cerevisiae, was evaluated for its ability to modify experimentally induced S. aureus septicemia in an immunosuppressed mouse model. AKR/J mice were injected with glucan (0.45 mg), cyclophosphamide (0.6 mg), isovolumetric saline (0.5 ml), or glucan (0.45 mg) and cyclophosphamide (0.6 mg) on days −10, −7, −4 and −1 prior to intravenous challenge with 1.0×109 S. aureus on day 0.
In contrast to the significant (P<0.05) decrease in leukocytes observed in the cyclophosphamide-treated mice, the administration of glucan to cyclophosphamide-treated mice resulted in maintenance of the peripheral leukocyte counts. Furthermore, glucan, as a single pretreatment regimen, resulted in a median survival time of 12.5 days, as against only 7.5 days in the saline control group. A 1.4-day median survival was observed in mice pretreated with cyclophosphamide and subsequently challenged with S. aureus. However, when glucan and cyclophosphamide were administered together, a median survival time of 9.0 days was observed.
Histopathologic examination revealed that glucan administration inhibited the renal necrosis observed in both normal and cyclophosphamide-treated mice following staphylococcal challenge. Glucan also produced a marked reduction of hepatic pathology in cyclophosphamide-treated mice following S. aureus challenge. These data denote that glucan administration is effective in altering morbidity and mortality due to systemic S. aureus disease in cyclophosphamide-treated mice.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ashworth, C. T., Di Luzio, N. R., Riggi, S. J.: A morphologic study of the effect of reticuloendothelial stimulation upon hepatic removal of minute particles from the blood of rats. Exp. Mol. Pathol. 1, 83 (1963)
Burgaleta, C., Golde, D. W.: Effect of glucan on granulopoiesis and macrophage genesis in mice. Cancer Res. 37, 1734 (1977)
Calabrisi, P., Parks, R. E.: Chemotherapy of neoplastic disease. In: The pharmacological basis of therapeutics, p. 1248. New York: McMillan 1975
Di Luzio, N. R.: Pharmacology of the reticuloendothelial system: Accent on glucan. In: The reticuloendothelial system in health and disease, p. 412. New York: Raven Press 1976
Di Luzio, N. R., Williams, D. L.: Protective effect of glucan against systemic Staphylococcus aureus septicemia in normal and leukemic mice. Infect. Immun. 20 (3), 804 (1978)
Di Luzio, N. R., McNamee, R. B., Browder, W. I., Williams, D. L.: Glucan: Inhibition of tumor growth and enhancement of survival in four syngeneic murine tumor models. Cancer Treat. Rep. 62 (11), 1857 (1978)
Fenselau, C.: Review of the metabolism and mode of action of cyclophosphamide. JAOAC 59, 1028 (1976)
Gaya, H., Tattersall, M. H. N., Hutchinson, R. M., Spiers, A. S. D.: Changing patterns of infections in cancer patients. Eur. J. Cancer 9, 401 (1973)
Glovsky,M. M., Di Luzio, N. R., Alenty, A., Ghekiere, L.: Complement activation by glucan. J. Reticuloendothel. Soc. 20, 54a (1976)
Golde, D. W., Burgaleta, C.: Glucan-activated macrophages: Functional properties and cytotoxicity against syngeneic leukemia cells. In: Immune modulation and control of neoplasia by adjuvant therapy, p. 201. New York: Raven Press 1978
Hassid, W. Z., Joslyn, M. A., McCready, R. M.: The molecular constitution of insoluble polysaccharide from yeast. J. Am. Chem. Soc. 63, 295 (1941)
Hoffmann, E. O., Di Luzio, N. R., Cook, J. A., McNamee, R. B., Armstrong, K.: The morphologic effects of glucan in the liver, lung, and spleen of the rat: Light and electron microscopic studies. Lab. Invest. 36, 340 (1977)
Hughes, W. T.: Fatal infections in childhood leukemia. Am. J. Dis. Child. 122, 283 (1971)
Hughes, W. T.: Infections in the compromised host. Adv. Intern. Med. 22, 73 (1977)
Israel, L., Edelstein, R.: Treatment of cutaneous and subcutaneous metastatic tumors with intralesional glucan. In: Immune modulation and control of neoplasia by adjuvant therapy, p. 249. New York: Raven Press 1978
Kokoshis, P. L., Williams, D. L., Cook, J. A., Di Luzio, N. R.: Increased resistance to Staphylococcus aureus infection and enhancement in serum lysozyme activity by glucan. Science 199, 1340 (1978)
Ladisch, S., Pizzo, P. A.: Staphylococcus aureus sepsis in children with cancer. Pediatrics 61, 231 (1978)
Lejeune, F. J., Delville, J., Gillet, J., Song, M., Stadtsbaeder, S., Jacques, P.: Effects of the yeast polysaccharide glucan on transplanted colon carcinoma of the rat and experimental infectious diseases: A preliminary report. Eur. J. Cancer (in press, 1978).
Mansell, P. W. A., Ichinose, H., Reed, R. J., Krementz, E. T., McNamee, R., Di Luzio, N. R.: Macrophage-mediated destruction of human malignant cells in vivo. J. Natl. Cancer Inst. 54, 571 (1975)
Mansell, P. W. A., Di Luzio, N. R., McNamee, R., Rowden, G., Proctor, J. W.: Recognition factors and non-specific macrophage activation in the treatment of neoplastic disease. Ann. N.Y. Acad. Sci. 277, 20 (1976)
Riggi, S. J., Di Luzio, N. R.: Identification of a reticuloendothelial stimulating agent in zymosan. Am. J. Physiol. 200, 297 (1961)
Sharbaugh, R. T.: Cyclophosphamide-induced immunosuppression and its effect on host resistance to bacterial invasion. Univ. of Mississippi Medical Center, Doctoral Thesis, p. 57 (1969)
Sharbaugh, R. T., Grogan, J. B.: Suppression of reticuloendothelial function in the rat with cyclophosphamide. Infect. Immun. 100, 117 (1969)
Sher, N. A., Chaparas, S. D., Greenburg, L. E., Bernard, S.: Effects of BCG, Corynebacterium parvum, and methanol-extraction residue in the reduction of mortality from Staphylococcus aureus and Candida albicans infection in immunosuppressed mice. Infect. Immun 12, 1325 (1975)
Sparks, F. C., Albert, N. E., Andreone, P. A., Breeding, J. H.: Effect of Bacillus Calmette-Guerin on immunosuppression from cyclophosphamide, methotrexate, and 5-fluoruracil. Cancer Res. 37, 2560 (1977)
Steven, M., Steven, P., Cook, J. A., Ichinose, H., Di Luzio, N. R.: Protective effect of the immunostimulant glucan on Sporotrichosis infections in mice. J. Reticuloendothel. Soc. 20, 66a (1976)
Williams, D. L., Cook, J. A., Hoffmann, E. O., Di Luzio, N. R.: Protective effect of glucan in experimentally induced candidiasis. J. Reticuloendothel. Soc. 23 (6), 479 (1978)
Wooles, W. R., Di Luzio, N. R.: Influence of reticuloendothelial hyperfunction on bone marrow transplantation. Am. J. Physiol. 203, 404 (1962)
Wooles, W. R., Di Luzio, N. R.: Reticuloendothelial function and the immune response. Science 142, 1078 (1963)
Wooles, W. R., Di Luzio, N. R.: The phagocytic and proliferative response of the reticuloendothelial system following glucan administration. J. Reticuloendothel. Soc. 1, 160 (1964)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Di Luzio, N.R., Williams, D.L. Glucan-induced modification of the increased susceptibility of cyclophosphamide-treated mice to Staphylococcus aureus infection. Cancer Immunol Immunother 6, 73–79 (1979). https://doi.org/10.1007/BF00200135
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00200135